• Korean Journal of Clinical Pharmacy
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• v.24 no.1
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• pp.15-25
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• 2014

Background: Elderly patients with gastrointestinal (GI) and cardiovascular (CV) risk factors may be more easily exposed to NSAID-related side effects (SEs). Based on the ACG guideline of year 2009, the aim of the study is to evaluate proper use of NSAIDs and gastroprotective drugs according to the degree of GI and CV risk strengths in the patients. Methods: Retrospectively surveyed 410 elderly patients with NSAIDs for more than 30 days at a general hospital in Korea. GI risk factor includes age, ulcer history, high-dose NSIADs, concurrent aspirin use, steroids or anticoagulants. CV risk factor includes angina, myocardial infarction, cerebral infarction, atrial fibrillation or coronary intervention requiring low-dose aspirin. These factors were classified as high/low cardiovascular groups and high/moderate/low GI groups. Results: There were 14 patients in high CV risk group and high GI risk group. The group was recommended not to use NSAIDs as it is not adequate. There were 101 patients in high CV risk group and moderate GI risk group. This group was recommended to use naproxen and PPI/misoprostol. But all patients except one were not adequate. There were 9 patients in low CV risk group and high GI risk group. This group was recommended to use selective COX-2 inhibitor and PPI/misoprostol. 5 cases were proper while 4 cases did not. There were 285 patients in low CV risk and moderate GI risk group who were recommended to use non selective NSAIDs and PPI/misoprostol or selective COX-2 inhibitor only. 103 patients were proper while 182 patients not adequate. Overall, the SEs were higher in those cases for inadequate use of drugs comparing to the adequate. CV SEs were statistically significant. However, SEs for each risk groups were different. For the case of low CV risk group and high/moderate GI risk group, the inadequate use of drugs makes the SE high and the other groups are not. Also, it was not statistically significant. Conclusions: In elderly patients, the inappropriate use of NSAIDs can increase the risk of the disease. Therefore, GI and CV risk must be considered simultaneously, and the proper use of NSAIDs and gastroprotective drugs for each risk groups should be reconsidered.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.18 no.4
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• pp.253-260
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• 2015

Purpose: The aim of the present study was to investigate the clinical features and outcome of eosinophilic gastroenteritis (EGE) in children. Methods: Our study enrolled 24 children who were diagnosed with EGE from 1993 to 2014 at the Department of Pediatrics, Seoul National University Children's Hospital. The patients' clinical manifestations, treatments, and outcomes were reviewed from the medical records. Results: The mean age at diagnosis was 5.3 years. Most patients had gastrointestinal symptoms including diarrhea (54.2%) and abdominal pain (45.8%). Peripheral eosinophilia was present in 91.7% of the patients. Thirteen patients (54.2%) showed anemia, and 15 patients (62.5%) had hypoalbuminemia. EGE was classified as mucosal, subserosal, or muscular in 75.0%, 20.8%, and 4.2% of cases, respectively. Three patients showed gastroduodenal ulcers upon endoscopic analysis. A history of allergy was reported in 13 patients, including atopic dermatitis, allergic rhinitis, and asthma. Five patients (20.8%) improved with food restrictions. Among the 19 patients treated with steroids, 11 (57.9%) discontinued steroid treatment without subsequent relapse, 4 (21.1%) relapsed after ceasing steroid treatment, and 4 (21.1%) showed no response to steroids. Two patients who were resistant to steroids underwent therapeutic surgery. The presence of gastroduodenal ulcers was significantly associated with relapse and steroid resistance. Conclusion: A high suspicion of EGE is warranted when children have nonspecific gastrointestinal symptoms and peripheral eosinophilia. Most patients improved with food restrictions or steroid treatment, although one-third of patients showed a relapse or steroid resistance.

• Journal of Food Hygiene and Safety
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• v.31 no.4
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• pp.286-293
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• 2016

This study is an experiment for gastric protective effects of ursolic acid. In order to identify the effects of ursolic acid on gastrointestinal disorder, acute and chronic gastritis were also observed using HCl ethanol and indomethacin-induced gastric lesion models, respectively. As for gastric acid, it was also identified through proton pump ($H^+/K^+-ATPase$) inhibiting activity. In regards to protective factor for gastric damage, prostaglandin $E_2$ ($PGE_2$) was quantitatively analyzed. Antibacterial activity experiment was done on Helicobacter pylori (H.pylori), which is known to be the causing factor of chronic gastritis, gastric ulcer and gastric cancer. By making use of AGS cell, it was confirmed that ursolic acid was involved in apoptosis of gastric cancer cell through 4',6-diamidino-2-phenylindol (DAPI) staining and flow cytometry analysis. As a result, ursolic acid reduced gastric lesions caused by HCl ethanol and indomethacin. Ursolic acid inhibited acid secretion by inhibiting proton pump ($H^+/K^+-ATPase$), which is the gastric acid secreting enzyme involved at the final phase of gastric acid secretion. And ursolic acid was identified with gastric mucosa protection effects by increasing the concentration of $PGE_2$, a protective factor of gastric mucosa preservation. The antibacterial activity on H. pylori, which is aggressive factor in gastrointestinal disorder, ursolic acid showed inhibitory effects on H. pylori colonization. In the DAPI nuclear staining, unlike the control group, shape of the nucleus has deformed, and has been observed either shrinked cell or chromatin condensation phenomenon. In the Flow cytometry assay, confirmed the growth rate of apoptosis in a concentration-dependent manner.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.5
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• pp.2351-2360
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• 2016

Management of Helicobacter pylori infection is an important aspect of many upper gastrointestinal tract diseases, such as chronic gastritis, peptic ulcer disease, gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma. The Thailand Consensus on H. pylori treatment 2015 consisted of 22 national experts who took active roles, discussed all important clinical information and investigated clinical aspects in four workshops, focuising on: (1) Diagnosis (2) Treatment (3) Follow-up after eradication and (4) H. pylori infection and special conditions. Experts were invited to participate on the basis of their expertise and contribution to H. pylori works and/or consensus methodology. The results of each workshop were taken to a final consensus vote by all experts. Recommendations were developed from the best evidence and availability to guide clinicians in management of this specific infection associated with variety of clinical outcomes.

• Journal of Gastric Cancer
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• v.1 no.4
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• pp.215-220
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• 2001

Purpose: The aim of the study was to obtain data on the anatomic and histologic distributions, the clinical features, and the treatment results for patients with primary gastric non-Hodgkin's lymphoma. Materials and Methods: One hundred thirty-two patients who were treated at 8 university hospitals and 2 general hospitals between January 1991 and December 2000 were enrolled to evaluate clinico-pathologic features. Results: The lower one-third of the stomach was the most frequent site ($42\%$), and the most frequent chief complaint was epigastric pain ($54\%$). Gastric resection was performed in 114 cases. Pathologic findings of preoperative endoscopic biopsy specimens from the 114 patients that underwent surgery were a gastric lymphoma in 94 cases ($82\%$), a carcinoma in 15 cases ($13\%$), an ulcer in 4 cases ($4\%$), and a gastrointestinal stromal tumor in 1 case ($1\%$). The stage distributions by Musshoff's criteria were 71 cases ($54\%$) of stage IE, 36 cases ($27\%$) of stage $II_{1}E$, 8 cases ($6\%$) of stage $II_{2}E$, 2 cases ($2\%$) of stage IIIE, and 15 cases ($11\%$) of stage IVE. Histologic gradings by the Working Formulation in were 31 cases ($23\%$) of low grade, 96 cases ($73\%$) of intermediate grade, and 5 cases ($4\%$) of high grade. Chemotherapy-related complications occurred in 25 cases ($22\%$) while operation-related complications occurred in 6 cases ($5\%$). Seventeen patients ($13\%$) only underwent surgery, 19 ($14\%$) had chemotherapy (CTx) and/or radiotherapy (RTx) only, and 96 patients ($73\%$) received surgery and CTx and/or RTx. No substantial differences in survival were found in relation to the different histologic grades and different treatments. The five-year survival was $85\%$ in stage I or II and $47\%$ in stage III or IV (P=0.0000). Conclusion: Pathologic stage appears to be the single most important prognostic indicator. Survival differences according to treatment modalities were not statistically significant. However, the low number of patients treated with various approaches over a long period precludes a firm conclusion.

• Korean Journal of Clinical Pharmacy
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• v.16 no.2
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• pp.155-164
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• 2006

Great inter-variability in drug response and adverse drug reactions is related to inter-variability of drug bioavailability, drug interaction and patient's disease and physyological state that cause change in absorption, distribution, metabolism and excretion of drugs. However, these alone do not sufficiently predict and explain inter-variability in drug response. In recent studies, it is reported that inter-variability in drug response and adverse drug reactions may largely resulted from genetically determined differences in drug absoption, distribution, metabolism and drug target proteins. Especially, the major human drug-metabolizing enzymes such as CYP450, N-acetyl tranferase, thiopurine S-methyl transferase, glutathione S-transferase are identified as the major gene variants that cause inter-individual variability in drug's response and adverse drug reactions. These variations may have most significant implications for those drugs that have narrow therapeutic index and serious adverse drug reactions. Therefore, the genetic variation such as polymorphisms in drug metabolizing enzymes can affect the response of individuals to drugs that are used in the treatment of depression, psychosis, cancer, cardiovascular disorders, ulcer and gastrointestinal disorders, pain and epilepsy, among others. This review describes the pharmacogenomics of the drug metabolizing enzymes associated with the drug response and its clinical applications.

• Korean Journal of Acupuncture
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• v.21 no.4
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• pp.101-115
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• 2004

Objective : The present studies investigated the effects of 120 Hz high frequency electroacupuncture (EA) on the stress-induced stomach dysfunction in relation to its effect on the level of stress hormones and gastric mucosal damages. The gastric mucosal injury was induced by cold-restraint stress and two acupoints corresponding to Zusanli and Sanyinjiao in man were used. Methods : Cold-restraint stress produced typical gastric lesions in all rats of the stressed groups, but the number of ulcers as well as the mean ulcer diameter were reduced by 120 Hz EA pre-treatment. Results : The degranulation value of gastric mast cell was significantly higher in cold-restrained rats than in control ones. However, with the significant reduction of degranulation values of gastric mast cells in EA pre-treated rats compared with cold-restrained rats. Cold-restarint stress induced an elevated mRNA expression of pro-inflammatory gene such as cyclooxygenases-2 and tumor necrosis factor $(TNF)-{\alpha}$, but these expression were down-regulated in EA pre-treated rats. Immunohistochemical analysis showed that while the $inhibitory-{\kappa}B{\alpha}$ and $TNF-{\alpha}$ immunorection in the surface epithelium of the stomach tended to increase, both reactions in the EA pre-treated rats showed similar pattern as observed in controls. Conclusion : These results suggest that 120 Hz EA may act as a therapeutical means for gastric mucosal damages through an activation of pituitary adrenal system. It could be concluded that 120 Hz high frequency electroaucupuncture affords a good protective potential against stress-induced gastrointestinal dysfunction.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.17 no.4
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• pp.223-231
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• 2014

Purpose: With previous methods based on only age and location, there are many difficulties in identifying the etiology of acute abdominal pain in children. We sought to develop a new systematic classification of acute abdominal pain and to give some helps to physicians encountering difficulties in diagnoses. Methods: From March 2005 to May 2010, clinical data were collected retrospectively from 442 children hospitalized due to acute abdominal pain with no apparent underlying disease. According to the final diagnoses, diseases that caused acute abdominal pain were classified into nine groups. Results: The nine groups were group I "catastrophic surgical abdomen" (7 patients, 1.6%), group II "acute appendicitis and mesenteric lymphadenitis" (56 patients, 12.7%), group III "intestinal obstruction" (57 patients, 12.9%), group IV "viral and bacterial acute gastroenteritis" (90 patients, 20.4%), group V "peptic ulcer and gastroduodenitis" (66 patients, 14.9%), group VI "hepatobiliary and pancreatic disease" (14 patients, 3.2%), group VII "febrile viral illness and extraintestinal infection" (69 patients, 15.6%), group VIII "functional gastrointestinal disorder (acute manifestation)" (20 patients, 4.5%), and group IX "unclassified acute abdominal pain" (63 patients, 14.3%). Four patients were enrolled in two disease groups each. Conclusion: Patients were distributed unevenly across the nine groups of acute abdominal pain. In particular, the "unclassified abdominal pain" only group was not uncommon. Considering a systemic classification for acute abdominal pain may be helpful in the diagnostic approach in children.

• Biomolecules & Therapeutics
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• v.11 no.3
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• pp.163-168
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• 2003

Pharmacokinetics of eupatilin (an active components of $Stillen^{\circledR}$, a new antigastritic agent) were investigated after both intravenous and oral administration at a dose of 30mg/kg to rats. After intravenous administration, the plasma concentrations of unchanged eupatilin declined rapidly with a mean terminal half-life of 0.101 h. Eupatilin was eliminated fast in rats; the total body clearance was 121 mL/min/kg. Eupatilin was mainly metabolized in rats; the percentage of intravenous dose of eupatilin excreted in 24 h urine and feces as unchanged eupatilin was only 2.5 and 0.919％, respectively. Eupatilin was mainly metabolized to form its glucuronide conjugate; after intravenous administration, 15.9 and 51.7％ of intravenous dose was excreted in 24 h urine and feces, respectively, as eupatilin plus its glucuronide. After oral administration, the absolute bioavailability was only 3.86％ based on $AUC_{0-24h}$ of eupatilin plus its glucuronide. Approximately 68.5％ of oral dose was not absorbed from the entire gastrointestinal tract. Therefore, it could be concluded that the superior effect of eupatilin in experimental animal models of gastric ulcer and inflammatory bowel disease after oral administration could be due to the local action of eupatilin. Further pharmacokinetic studies to elucidate the local action of eupatilin are required.

• Journal of Pharmaceutical Investigation
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• v.15 no.2
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• pp.53-62
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• 1985

Pivampicillin hydrochloride is a kind of broad spectrum antibiotics with bactericidal action, and is used in many countries, although it has bitter taste, unpleasant odour and side effects of irritating gastric mucosa, nausea, penicillin allergy, etc. For the improvement of such side effects of pivampicillin hydrochloride, microcapsules, with wall of ethylcellulose, have been prepared by coacervation method. The shape was observed through the scanning electron microscope, the release of the drug into an aqueous medium was studied and the effects of core: ethylcellulose ratio were interpreted as well as making sensory evaluation of taste and odour. There was decreasing trend in dissolution rate of the drug with the increase of core: ethylcellulose ratios, and the smaller microcapsules released their contents more rapidly. A linear relationship was established between the amount of ethylcellulose and the time for 60% release of the drug, and the release pattern was found to have similar characteristics to the release of the drug from an insoluble porous matrix. The release of the drug in the artificial intestinal fluids (pH 6.8) was found to be similar to that in water, while the release in the artificial gastric juice (pH 1.2) was slightly slower. Bioavailability of microcapsule was compared with that of pivampicillin hydrochloride in rabbits using serum concentration and urinary excretion measurements. Microcapsule gave showed slightly higher serum level than pivampicillin hydrochloride from 2 hours after administration, while no significant difference was observed in the accumulated urinary excretion rate between pivampicillin hydrochloride and microcapsule. The ulcer index of pivampicillin hydrochloride administered group was 2.6, and microcapsule administered group was 1.5, while control group was 0.8. Therefore it may be concluded that microencapsulation of pivampicillin hydrochloride is a useful pharmaceutical approach to protect the gastrointestinal tract from being injured by direct contact of pivampicillin hydrochloride without any significant difference of bioavailability.